Prostate cancer is the most frequently diagnosed male cancer and the second-leading cause of oncological mortality in men living in the United States [
1]. It is a clinically heterogeneous, multifactorial disease and the incidence is continuously rising. Like many other solid tumors, prostate cancer mortality attributes largely to cancer metastasis, a complicated process that involves changes in the extracellular matrix to support invasion, increased cell motility and the ability of cells to initiate and maintain growth at a distant site [
2]. However, unlike a majority of solid cancers, prostate cancer usually shows poor response to chemotherapy. Therefore, more effective strategies for the targeted treatment of prostate cancer, especially for cancer metastasis, are urgently needed.
Carcinogenesis and progression are multistep processes, involving numerous genetic mutations, aberrant gene expression, and microRNA (miRNA) dysregulation [
3]. MicroRNAs (miRNAs), which are widespread in eukaryotic cells, are endogenous single stranded, non-protein-coding RNAs of approximately 22 nucleotides in length. Numerous cellular processes are affected by miRNA, including differentiation, proliferation, cell-cycle control, apoptosis, migration and invasion [
4]. miRNAs exert their regulatory effects by binding to partially complementary sequences in the 3′-untranslated region (3′UTR) of target mRNAs, reducing the stability and/or translation efficiency of target mRNAs in a sequence-specific manner. Accumulating evidence suggests that miRNAs are significant molecules in diverse cancers, including prostate cancer, by regulating the expression of various oncogenes and tumor suppressors [
5,
6]. Large scale miRNA expression analyses indicated a common deregulation of miRNAs in tumors compared to their benign counterparts. For example, in the prostate cancer miRNA signature analysis carried out by Porkka et al. [
7], expression profiling of 319 miRNAs in 6 prostate cancer cell lines, 9 prostate cancer xenografts samples, and 13 clinical prostate tissue samples were used to classify prostate tumors. Here, 37 miRNAs (miR-16, miR-23a, miR-23b, miR-143, miR-145, miR-195,miR-221, miR-222, miR-497 et al.) were found to be downregulated in hormone-refractory late-stage prostate carcinomas, whereas 14 miRNAs were upregulated in hormonerefractory carcinomas. Schaefer et al. [
8] validated that ten microRNAs (hsa-miR-16, hsa-miR-31, hsa-miR-125b, hsa-miR-145, hsa-miR-149, hsa-miR-181b, hsa-miR-184, hsa-miR-205, hsa-miR-221, hsa-miR-222) were downregulated and five miRNAs (hsa-miR-96, hsa-miR-182, hsa-miR-182, hsa-miR-183, hsa-375) were upregulated in prostate cancer. Meanwhile, several miRNAs were also shown to be deregulated and functionally relevant across different cancer diseases: down-regulation of miR-125a and miR-125b in breast cancer [
9], the let-7 miRNAs in lung cancer [
10], and miR-143 and miR-145 in different cancer types [
11]. Besides, further investigations have assessed the diagnostic and prognostic value of miRNA profiling in prostate cancer. Of note, two promising miRNAs, miR-141 and miR-375, were suggested as diagnostic and prognostic marker across independent studies. Both miRNAs were found to be elevated in serum of men with metastatic castration-resistant prostate cancer compared to healthy individuals [
12,
13]. To elucidate the role of the individual miRNAs in prostate cancer, genes and pathways which are regulated by the differentially expressed miRNAs should be studied. Thus, a set of targets of miRNAs have been identified in relevant studies. The restoration of miR-205 has been shown to restrain cell viability via targeting MED1, miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells, miR -23b represses proto-oncogene Src kinase, miR-125a and miR-125b suppress the oncogenes ERBB2 and ERBB3 [
14‐
17]. Although the study of miRNAs is still challenging due to variable downstream regulators, the above evidence gives us a promising outlook for the application of miRNAs for prostate cancer management.
Several recent studies have presented a global analysis of miR-195 expression and function in different human cancers. Our previous study showed that overexpression of miR-195 could induce G1-phase arrest by targeting the novel target CDK4 in bladder cancer cells [
18]. It was reported that miR-195 could block the G(1)/S transition in hepatocellular carcinoma cells by repressing Rb-E2F signaling through targeting multiple molecules, including cyclin D1, CDK6, and E2F3 [
19]. miR-195 played a tumor-suppressor role in human glioblastoma cells by targeting E2F3 and CCND3 involved in cellular proliferation and invasion [
20]. Besides, it also promoted colorectal cancer cell apoptosis by repressing Bcl-2 [
21]. In the current study, we aimed to determine the role of miR-195 in determining the aggressiveness of prostate cancer cells and studied the correlated regulatory mechanism of miR-195. We found that miR-195 expression was downregulated in two prostate cancer cell lines, ectopic expression of miR-195 significantly suppressed cell migratory and invasive capacities of PC3 and DU145 cells through inhibition of Fra-1. These findings indicated that miR-195 could be a potential tumor suppressor by directly binding to Fra-1 in prostate cancer.